Photoacoustic (PA) imaging is based on the detection of acoustic signals induced by the distribution of specific optical heterogeneities in targeted objects when irradiated by short laser pulses. Contrast in PA images is primarily determined by optical absorption, but spatial resolution is the same as in ultrasound. This contrast capability within deep biological tissue cannot be achieved by pure optical or ultrasound imaging, which both depend primarily on wave scattering mechanisms. Given the megahertz (MHz) range of acoustic signals processed in PA imaging, sub-millimeter resolution is possible for routine clinical applications.
Photoacoustics is very attractive for molecular imaging because optical absorption is an efficient way to detect and differentiate specific molecules from other components. By designing a specific wavelength selective absorption contrast agent, PA imaging can provide high sensitivity and specificity to molecular targets. By coupling specifically designed molecular contrast agents to particular biological objects such as cancer cells, targeted cells can be specifically differentiated from the background.
However, when visualization of targeted molecules is necessary in the vasculature, PA imaging is severely challenged by the large optical absorption of hemoglobin even within the therapeutic window of optical radiation. The strong PA background signal from blood can mask contrast agents and make quantitative measurements of molecular concentration very difficult, especially for low concentrations of contrast agents.
The PA signal from a targeted contrast agent can be increased relative to the background by increasing its concentration, especially in model systems such as mice, but in humans potential toxicity limits increases in contrast agent concentration. Furthermore, in certain applications, such as in rare cell detection, this is not feasible. Indirect enhancement of the PA signal from the targeted object is much more desirable.
One method to suppress the background relative to a targeted contrast agent is to use PA measurements at multiple wavelengths to differentiate the contrast agent absorption signature from that of the background. Promising results have been achieved recently in multicolor PA tomography. The main drawback of this approach is the difference in light scattering at different wavelengths. In particular, the distribution of laser fluence inside the object under study cannot be considered the same at different wavelengths. This makes solution of the inverse problem quite ambiguous.
U.S. Patent Application Publication No. US 2011/0117028 describes a two-wavelength approach using multiple contrast agents to identify magnetically trapped circulating tumor cells using PA imaging. However, such an approach will be difficult to translate into the clinic because it uses multiple types of nanoparticles and a multi-wavelength system requiring careful in situ calibration to ensure sufficient suppression of the background blood signal.
Despite the advances in photoacoustic imaging noted above, a need exists to provide a method and device for suppressing background signal in magneto-motive photoacoustic imaging of magnetic contrast agents in complex systems. The present invention seeks to fulfill this need and provides further related advantages.